(−)N-(Chloroethyl)norapomorphine inhibits striatal dopamine function via irreversible receptor binding

Abstract

β-Haloalkylamine derivatives such as phenoxybenzamine are thought to irreversibly inactivate noradrenaline receptors by a process involving the formation of a reactive ethyleneimmonium cation which is followed by ring scission yielding the reactive carbonium ion which can then react further with a nucleophilic centre located on the receptor. Further study of catecholamine function has awaited the development of similar agents which can alkylate the dopamine receptor. We report here on the structure (Fig. 1) and evaluation of one agent with such potential, (−)N-(chloroethyl)norapomorphine [(−)NCA], and that this compound may be of significant value as a pharmacological and biochemical probe of the dopamine receptor.